title: Contribution of renal purinergic receptors to renal vasoconstriction in angiotensin II-induced hypertensive rats.
abstract: To investigate the participation of purinergic P2 receptors in the regulation of renal function in ANG II-dependent hypertension, renal and glomerular hemodynamics were evaluated in chronic ANG II-infused (14 days) and Sham rats during acute blockade of P2 receptors with PPADS. In addition, P2X1 and P2Y1 protein and mRNA expression were compared in ANG II-infused and Sham rats. Chronic ANG II-infused rats exhibited increased afferent and efferent arteriolar resistances and reductions in glomerular blood flow, glomerular filtration rate (GFR), single-nephron GFR (SNGFR), and glomerular ultrafiltration coefficient. PPADS restored afferent and efferent resistances as well as glomerular blood flow and SNGFR, but did not ameliorate the elevated arterial blood pressure. In Sham rats, PPADS increased afferent and efferent arteriolar resistances and reduced GFR and SNGFR. Since purinergic blockade may influence nitric oxide (NO) release, we evaluated the role of NO in the response to PPADS. Acute blockade with N(ω)-nitro-l-arginine methyl ester (l-NAME) reversed the vasodilatory effects of PPADS and reduced urinary nitrate excretion (NO(2)(-)/NO(3)(-)) in ANG II-infused rats, indicating a NO-mediated vasodilation during PPADS treatment. In Sham rats, PPADS induced renal vasoconstriction which was not modified by l-NAME, suggesting blockade of a P2X receptor subtype linked to the NO pathway; the response was similar to that obtained with l-NAME alone. P2X1 receptor expression in the renal cortex was increased by chronic ANG II infusion, but there were no changes in P2Y1 receptor abundance. These findings indicate that there is an enhanced P2 receptor-mediated vasoconstriction of afferent and efferent arterioles in chronic ANG II-infused rats, which contributes to the increased renal vascular resistance observed in ANG II-dependent hypertension.
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, México City, Mexico. marthafranco@lycos.com
authors.forename: Martha
authors.initials: M
authors.lastname: Franco
authors.forename: Rocio
authors.initials: R
authors.lastname: Bautista
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.forename: Virgilia
authors.initials: V
authors.lastname: Soto
authors.forename: José
authors.initials: J
authors.lastname: Santamaría
authors.forename: Horacio
authors.initials: H
authors.lastname: Osorio
authors.forename: Ursino
authors.initials: U
authors.lastname: Pacheco
authors.forename: L Gabriela
authors.initials: LG
authors.lastname: Sánchez-Lozada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058474:Receptors, Purinergic P2X1 / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D058474:Receptors, Purinergic P2X1; D058472:Receptors, Purinergic P2Y1; D000804:Angiotensin II; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester